Dancing with the Diva: Hsp90-Client Interactions

Publication date: Available online 18 May 2018 Source:Journal of Molecular Biology Author(s): Martina Radli, Stefan G.D. Rüdiger The molecular chaperone Hsp90 is involved in the folding, maturation and degradation of a large number structurally and sequentially unrelated clients, often connected to serious diseases. Elucidating the principles of how Hsp90 recognises this large variety of substrates is essential for comprehending the mechanism of this chaperone machinery, as well as it is a prerequisite for the design of client specific drugs targeting Hsp90. Here, we discuss the recent progress in understanding the substrate recognition principles of Hsp90 and its implications for the role of Hsp90 in the lifecycle of (signalling) molecules. Hsp90 acts downstream of the chaperone Hsp70, which exposes its substrate to a short and highly hydrophobic cleft. The subsequently acting Hsp90 has an extended client binding interface that enables a large number of low-affinity contacts. Structural studies show interaction modes of Hsp90 with the intrinsically disordered Alzheimer's disease-causing protein Tau, the kinase Cdk4 in a partially unfolded state and the folded ligand-binding domain of a steroid receptor. Comparing the features shared by these three different proteins provides a picture of the substrate-binding principles of Hsp90. Graphical abstract
Source: Journal of Molecular Biology - Category: Molecular Biology Source Type: research